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Synchronous versus sequential chemo-radiotherapy in patients with early stage breast cancer (SECRAB): A randomised, phase III, trial

Fernando, Indrajit N.; Bowden, Sarah J.; Herring, Kathryn; Brookes, Cassandra L.; Ahmed, Ikhlaaq; Marshall, Andrea; Grieve, Robert; Churn f, Mark; Spooner, David; Latief, Talaat N.; Agrawal, Rajiv K.; Brunt, Adrian M.; Stevens, Andrea; Goodman, Andrew; Canney, Peter; Bishop, Jill; Ritchie, Diana; Dunn, Janet; Poole, Christopher J.; Rea, Daniel W.

Synchronous versus sequential chemo-radiotherapy in patients with early stage breast cancer (SECRAB): A randomised, phase III, trial Thumbnail


Authors

Indrajit N. Fernando

Sarah J. Bowden

Kathryn Herring

Cassandra L. Brookes

Ikhlaaq Ahmed

Andrea Marshall

Robert Grieve

Mark Churn f

David Spooner

Talaat N. Latief

Rajiv K. Agrawal

Andrea Stevens

Andrew Goodman

Peter Canney

Jill Bishop

Diana Ritchie

Janet Dunn

Christopher J. Poole

Daniel W. Rea



Abstract

BACKGROUND: The optimal sequence of adjuvant chemotherapy and radiotherapy for breast cancer is unknown. SECRAB assesses whether local control can be improved without increased toxicity. METHODS: SECRAB was a prospective, open-label, multi-centre, phase III trial comparing synchronous to sequential chemo-radiotherapy, conducted in 48 UK centres. Patients with invasive, early stage breast cancer were eligible. Randomisation (performed using random permuted block assignment) was stratified by centre, axillary surgery, chemotherapy, and radiotherapy boost. Permitted chemotherapy regimens included CMF and anthracycline-CMF. Synchronous radiotherapy was administered between cycles two and three for CMF or five and six for anthracycline-CMF. Sequential radiotherapy was delivered on chemotherapy completion. Radiotherapy schedules included 40?Gy/15F over three weeks, and 50?Gy/25F over five weeks. The primary outcome was local recurrence at five and ten years, defined as time to local recurrence, and analysed by intention to treat. ClinicalTrials.gov NCT00003893. FINDINGS: Between 02-July-1998 and 25-March-2004, 2297 patients were recruited (1150 synchronous and 1146 sequential). Baseline characteristics were balanced. With 10.2 years median follow-up, the ten-year local recurrence rates were 4.6% and 7.1% in the synchronous and sequential arms respectively (hazard ratio (HR) 0.62; 95% confidence interval (CI): 0.43-0.90; p?=?0.012). In a planned sub-group analysis of anthracycline-CMF, the ten-year local recurrence rates difference were 3.5% versus 6.7% respectively (HR 0.48 95% CI: 0.26-0.88; p?=?0.018). There was no significant difference in overall or disease-free survival. 24% of patients on the synchronous arm suffered moderate/severe acute skin reactions compared to 15% on the sequential arm (p?<?0.0001). There were no significant differences in late adverse effects apart from telangiectasia (p?=?0.03). INTERPRETATION: Synchronous chemo-radiotherapy significantly improved local recurrence rates. This was delivered with an acceptable increase in acute toxicity. The greatest benefit of synchronous chemo-radiation was in patients treated with anthracycline-CMF. FUNDING: Cancer Research UK (CR UK/98/001) and Pharmacia.

Journal Article Type Article
Acceptance Date Oct 20, 2019
Online Publication Date Nov 27, 2019
Publication Date 2020-01
Publicly Available Date Mar 28, 2024
Journal Radiotherapy and Oncology
Print ISSN 0167-8140
Publisher Elsevier
Volume 142
Pages 52-61
DOI https://doi.org/10.1016/j.radonc.2019.10.014
Keywords Breast cancer, Chemo-radiotherapy, Clinical trial, Radiotherapy
Publisher URL https://doi.org/10.1016/j.radonc.2019.10.014

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